P1466: CD7 CHIMERIC ANTIGEN RECEPTOR T CELLS FOR ADULT PATIENTS WITH REFRACTORY AND RELAPSED T CELL MALIGNANCIES
Authors: Y. Zhang, W. Luo, C. Li, M. Du, F. Zhou, L. Tang, J. Wu, H. Jiang, Q. Wei, C. Lu, H. Kou, D. Wu, A. H. Chang, Y. Hu, H. Mei
Journal: HemaSphere (2022)

Background: Although first-line chemotherapies had a satisfying response in primary T cell malignancies, those with refractory or relapsed diseases still presented dismal outcomes, especially in adults. CD7 is a potential target highly expressed both in malignant and normal T cells. CD7-knockout anti-CD7 CAR-T cells have been proven effective in pediatric T-ALL, but its administration in adult patients has not been reported. Aims: This study aims to evaluate the safety and efficacy of anti-CD7 CAR-T cells in adults with R/R T cell malignancies and the distinctions between autologous and allogeneic CAR-T cells. Methods: In this trial (NCT04823091), anti-CD7 CAR T cells were manufactured from HLA-matched sibling donors or autologous mononuclear cells and administrated to 10 participants at a dose of 1×106 (n=5) or 2×106 (n=5) cells/kg. The primary endpoint was safety with efficacy secondary. Four participants were chosen to match patients receiving CD19 CAR-T according to their baselines. Both CAR-T had humanized antigen recognition and 4-1BB costimulatory. Subtype and expression of immune checkpoints of infusion products were detected. Results: Ten patients received CAR-T cells after lymphodepleting chemotherapy, five with autologous and five with allogenic CAR-T. Adverse events including cytokine release syndrome grade 1-2 occurred in 70% and grade 3-4 in 10%, cytopenia grade 4 in 100%, graft-versus-host disease grade 1-2 in 20% and multiple infections in 60%. No neurotoxicity was observed (Figure 1B). All adverse events were reversible after prompt treatment, except in one patient who died of fungal pneumonia at 2.5 months. As of Feb 22, 2022, the median follow-up was 4 months (range 2-9.5). Eight patients responded to CAR-T therapies and 100% (n=6) of patients achieved MRD-negative hematological remission. Extramedullary lesions were eliminated partially in 80% of 5 patients. Pt1 with mycosis fungoides bridging lradiation obtained a long-term CR over 9.5 months (Figure 1A). CD7 CAR T-cells expanded to peak level at 14 days (7-23) post-infusion and persisted in a small quantity for up to 4 months (Figure 1C). A transient reduction of lymphocytes was observed in all patients and recovered in about one month with CD7-negative. There was no difference in the proportion of cell subtypes and expression of exhausted biomarkers between CD7- and CD7+ T cells. There was a greater likelihood of developing mild CRS and prolonged leukopenia in the allogenic group, which could be resolved spontaneously. The administration of allogenic CAR-T did not increase the risk of viral infection or GVHD. Patients in two groups presented the same overall response rate but a higher possibility of complete remission was observed in allogenic ones. Peak numbers of CAR-T cells were not associated with the origins of T cells. CD7 CAR-T cell contained significantly lower percentages of CD8+T cells (P=0.0017), naive T cells (P=0.0477), higher percentages of Treg (P=0.0206), effector memory T cells (P=0.018), and CTLA-4 positive T cells (P=0.0226) compared to CD19 CAR-T (Figure 1D). The characters of CAR-T cell phenotypes may explain the significant reduction of CD7 CAR-T cells in one month. Image:Summary/Conclusion: These results show that CD7 CAR-T cells can produce anti-tumor responses with relatively controlled adverse events. Auto- or allo-CAR-T have similar efficacy and safety in the process, thus optimal solutions can be selected depending on their situations. CD7 CAR-T presents a potential therapeutic option for adults with R/R T cell malignancies, but the long-term prognosis remains to be observed and improved.